25

Book Reviews

        Six books on Cannabis, published in the US and Canada in 1998 and 1999, will be reviewed. The Institute of Medicine Report, issued in March 1999, has gathered the most world-wide attention (Joy et al. 1999). A chapter of the second book, a comparison of the health effects of Cannabis with alcohol, nicotine and opiates, led to a controversial discussion in spring 1998 and is now published along with 14 other papers on the health effects of Cannabis (Kalant et al. 1999). The third and largest book covers a conference on "Marihuana and Medicine" in May 1998 in New York, edited by scientists that oppose the medical use of Cannabis (Nahas et al. 1999). The fourth is a practical guide for patients, written by three physicians who are promoting legal access to medical marijuana (Zimmermann et al. 1998). The fifth, written by a journalist, describes the US Governments handling of the marijuana issue and accuses them of dishonesty by focusing mostly on recreational use (Ford 1998). The sixth has been written by a marijuana patient who is describing the political and scientific discussion in the US over the last 25 years from a personal point of view (Randall and O’Leary 1998).

        Joy, J. E., Watson, S. J., Benson, J.A (eds): Marijuana and Medicine: Assessing the Science Base.
         Institute of Medicine, National Academy Press, Washington DC, 1999, 290 pages
         On 17 March 1999, Stanley Watson, Co-director and research scientist, Mental Health Research Institute, University of Michigan, and John Benson, Dean and Professor of medicine emeritus, Oregon Health Sciences University, presented the second Institute of Medicine Report (IOM) on marijuana, the first being published in 1982. It was ordered by the White House Office of National Drug Control Policy in January 1997 as a reaction to successful ballot state initiatives in California and Arizona in November 1996, allowing the medical use of marijuana for seriously ill patients. The thorough and factual reports say that marijuana is potentially effective for some symptoms and recommends rigorous clinical trials and the development of a delivery system that eliminates the harmful effects of smoking. Beyond the harms of smoking, the range of problems associated with medical marijuana were within the acceptable range of problems associated with other medications. Further, it states that marijuana could be allowed for medical use, without increasing non-medical use. The authors say there is "no convincing data to support this concern," and they note that "this question is beyond the issues normally considered for medical uses of drugs." It makes six recommendations, including clinical trials allowing patients with chronic conditions or end-stage diseases, who have no other alternative, to use marijuana on an experimental basis for six months.
        The assertation of the IOM report that single cannabinoids are more suitable for reproducing the desired therapeutic effects than the whole plant is irritating for a reader from a country where the use of herbal products is widespread in medicine. It has not much to do with reality. Neither THC nor Nabilone act more selectively than a standardised extract of the Cannabis plant. The idea of pure agents for a specific effect is a dream of medical science never realised until now. Drug therapy always has to do with interindividual and intraindividual variability of a lot of parameters: age, gender, general health status, concomitant disease, interaction with other drugs, resorption, function of spleen and liver etc. There is no hint that the variability of the components of Cannabis with the exception of THC and CBD plays a major role in the reproducibility of effects in comparison to these and other parameters.
        However, the new IOM-Report is a valuable review on the matter and understandable by non-scientists. It presents the political background, examples of successful medical uses of the drug, the pharmacology and animal physiology, the consequences and side-effects of marijuana use, the medical value of marijuana and related substances and the development of cannabinoid drugs.

        Kalant, H., Corrigal, W. A., Hall, W., Smart, R. G.: The health effects of Cannabis.
         Centre for Addiction and Mental Health, Toronto, Canada, 1999, 540 pages.
         One of the 15 chapters of the book raised much interest and controversy about one year before it was published. It was only available as a manuscript then, as one of the background papers for the Cannabis report of the World Health Organization of December 1997 ("Cannabis: a health perspective and research agenda"). According to the New Scientist of February 1998, officials of the WHO in Geneva had suppressed the paper, because when comparing the health effects and psychological risks of alcohol, Cannabis, nicotine, and opiate use, it had shown the lowest risk for Cannabis. The WHO claimed in reply to the reproach of censorship, that this part was not included in the WHO review due to scientific reasons. Another chapter evoked some media resonance in the beginning of this year when the entire collection of papers was published as a book, edited by Wayne Hall, head of the Australian National Drug and Alcohol Research Centre, and scientists of the Canadian Addiction Research Foundation. It was the chapter on "Marijuana: on-road and driving simulator studies" by Alison Smiley. She had told the press that people who smoke moderate amounts of marijuana were not much more dangerous behind the wheel than completely sober drivers, because people under the influence of Cannabis would compensate for their impaired performance by driving more slowly and cautiously.
        People who want to get an overview of the chemistry, pharmacology and possible adverse effects of Cannabis will find in these articles well-balanced information on the relevant discussion lines and a good review of the most important primary literature. Articles deal with the influences of Cannabis on different body systems and functions, the central nervous system, behaviour, cell nuclei, immunity, respiratory system, reproductive function, pregnancy, the cardiovascular and the gastrointestinal system. Conclusions are usually not final but rather an intermediate description which tries not to fall into the trap of "problem inflation" and "problem deflation", in cases where our knowledge is still limited. The book is a valuable reference and review, as are earlier reviews initiated by governmental institutions or international organisations, the two Institute of Medicine reports (1982, 1999), the Australian report by Hall, Solowij and Lemon (1994) and the WHO report of 1981 (Fehr and Kalant, 1983).
        People who want to get an overview of the medical use of Cannabis will be disappointed. If science aims to get an image of the world, this chapter documents that science has failed to a great extent in assessing the therapeutic potential of Cannabis and the cannabinoids. And it demonstrates what happens when experience on a therapeutic topic is drawn only from printed paper and not from contact with patients. What is presented by Christine R. Hartel is a very limited and reserved look at the issue. This leads to the strange situation that there are patients with multiple sclerosis, Tourette’s syndrome, epilepsy, glaucoma, and other illnesses that have strong relief from Cannabis, confirmed by many physicians and that on the other hand you will read in this chapter "that THC and marijuana are not considered candidates for drug development for this indication," or that "further controlled research is indicated before conclusions can be drawn". The reader will miss some interesting studies in this 10 page review, the study by Brenneisen and colleagues (1996) on spasticity, the study by Holdcroft et al. (1997) on pain and the study by Volicer (1997) on Alzheimer’s disease.
        Hartel takes adverse effects due to the illegal status of Cannabis as arguments against legal medical access: Smoking causes harm, plant material may be contaminated, potency may be variable. These problems would not exist if there were a legal supply of standardised Cannabis which could be inhaled by the use of vaporisers that are already available. In sum, the book provides a limited picture of the medical use of Cannabis.
        But it provides a valuable overview on its pharmacology and toxicology. It is much recommended for people who want to get a more than superficial overview and a deeper insight into the research of the last three decades and the actual discussion.

        Nahas, G., Sutin, K. M., Harvey, D. J., Agurell, S.: Marihuana and Medicine.
         Humana Press, Totowa, NY, 1999, 848 pages.
         This is a collection of papers mostly concerned with "the pharmacological and molecular basis of the therapeutic properties of marihuana and its active ingredient, THC" as explained in the books introduction. The popular topic "therapeutic properties of marihuana" seems to be used (or misused) to present, above all, the real, presumed or pretended dangers connected with the recreational use of Cannabis. The book follows the conference of the International Cannabinoid Research Society on "Marihuana and Medicine" in May 1998 at New York University School of Medicine, headed by Gabriel Nahas, a well-known opponent of the medical use of marijuana.
        Relevant and not so relevant information, reviews and original articles are mixed up in a book covering 850 pages. We find a text on "Suppression and induction of aggressive reactions by chronic and acute (delta-9-tetrahydrocannabinol) treatment in laboratory rats" or on the "Detection of Cannabis in victims of violent death in Stockholm" which looks rather strange in a book that claims to present the basis for the therapeutic use of the drug. To cite the IOM report these topics are "beyond the issues normally considered for medical uses of drugs."
        These and many other chapters give the whole book a rather sceptical look concerning the topic without analysing their relevance for the therapeutic situation in humans. The unprepared reader will sometimes be more led astray than well-informed. But there are many other relevant and well-presented articles, e.g. on the mechanisms of analgesia, control of nausea and vomiting and other effects, which are interesting for those who want to get a deeper insight into the issue and are able to separate the relevant from irrelevant information.

        Zimmermann, B., Bayer, R., Crumpacker, N.: Is marijuana the right medicine for you.
         Keats Publishing, New Canaan, Conneticut, 1998, 208 pages.
         The book focuses on the practice of the medical use of natural Cannabis and THC, intending to give people a step-by-step introduction to the topic, giving answers to questions that might arise. Twelve of the 20 chapters deal with indications (AIDS, glaucoma, nausea, multiple sclerosis etc.), the others with possible adverse effects, practical hints for getting and using marijuana and the political discussion. It is perceivable that it is written by physicians that have practical experience in the assistance of patients, among them Bill Zimmermann, director of Americans for Medical Rights which fights for access to medical marijuana. The authors take the experience of patients seriously and are ready to learn from them, citing the motto of a medical school: "The patient is the text book". It is really "a factual guide to medical uses of marijuana". The authors neither exaggerate the medical value of the plant in terms of "wonder" or "miracle", that often leads to disappointment in patients if marijuana should not work, nor do they undervalue the medical quality solely because a certain effect, that is well known by hundreds of patients and physicians, has not been proven in a randomised double-blind trial.
        Concerning some possible long-term effects the book is sometimes too definite, regarding the ongoing discussion in this area. This may be in part due to limited space and to the wish to not bother the reader with a complex discussion. There are some points that might be considered in the next edition, e.g. in the part on sterilising marijuana it is said that 190(C (374(F) should not be exceeded in this process, but it was found in a study by Brenneisen and colleagues, that a temperature of 200oC for five to ten minutes seems to be the optimum temperature for the decarboxylation of THC-acid. So there is no need for a strong warning.
        I do recommend this book very much. It is one of the best of those written to help patients get an introduction and overview of the medical usefulness of Cannabis products and how to use them.

        Ford, D. R.: Marijuana: not guilty as charged.
        Good Press, Sonoma, California, 1998, 253 pages.
         This book is a plea for the legalisation of marijuana for medical and recreational use. The author describes the hypocrisy, stupidity and cruelty of marijuana policy in the United States through a series of unrevealing stories and well known and less well known documents. They demonstrate the ignorance of arguments and the harmful consequences of marijuana prohibition. The reader develops a feeling of rage and powerlessness on a culture of the Middle Ages where revenge rules and rationality still has no place.
        There is a strong tendency in the book to mix the medical and the recreational use and to use or misuse patients with severe illnesses as an example of the cruelty of the war on drugs. ("The ill and the dying are the primary losers when it comes to marijuana prohibition."). It is a book that tries to move emotions, not shrinking from using the strongest phrases and the most dramatic comparisons ("the slaughter of marijuana"). Possible side effects are generally minimised ("Marijuana is not any more physically addictive than ice-cream"). I am always irritated about this way to aggravate or minimise and it makes me sceptical about the honesty of the author. Mutual irrationality seems to be typical for both sides in the war on drugs. Could it be that the inflationary use of extreme comparisons and allegories and the low practice of differentiating on both sides of the discussion is a cause for some complications in the struggle for the reintroduction of Cannabis as a medicine and Cannabis as a crop? This book leaves you with a very mixed impression.

        Randall, R. C., O’Leary, A. M.: Marijuana RCS: the patients’ fight for medicinal pot.
         Thunder’s Mouth Press, New York, 1998, 498 pages.
         The book by Robert Randall, the first American to get legal access to medical marijuana in 1976, and his partner Alice O’Leary tells the story about 25 years of struggle for legal access to the therapeutic use of Cannabis in the US. In 40 chapters the beginnings of the movement, the first changes of state laws, the introduction of Marinol®, the foundation of organisations advocating the medical use of marijuana and the hopes and tragedies are presented in a narrative and tightening way.
        The open manner that does not stop short of criticising exponents of the marijuana movements gives the reader a deep insight into different aspects of the developments in the last decades. He is not only attacking the governmental institutions and judges that deny patients marijuana for therapeutic purposes but also exponents and organisations of the marijuana movement, that in the eyes of Randall misuse the medical issue for drug policy ("Drug ideologues to the left and right."). Most of the book is biographical with a lot of lively dialogues that describe the experiences of ups and downs within the long struggle of the co-founders of the Alliance for Cannabis Therapeutics.
        Worth mentioning is the foreword of Lyn Nofziger, former White House director of communication and chief speech writer for Ronald Reagan. Telling a story from his family he promotes the medical use of marijuana. "Strange as it may seem, here is one right-wing Republican who supports carefully controlled, medical access to marijuana. (...) A doctor should have every possible medication — including marijuana — in his armentarium."
        I enjoyed reading the book. I do not know if it tells the "truth about the patients’ fight for medical pot", as is claimed in the advertisement, but at least it tells of one which is worth reading and knowing about.

        Franjo Grotenhermen
        nova Institute
        Huerth in the Rhineland, Germany

        Dissertation by Birgitte de Groot: A thesis success-fully defended by the respondent at the oral dissertation on Oct. 10th 1998 in partial fulfillment for the doctor degree in Chemical Engineering at the University of Agriculture in Wageningen, The Netherlands.
        An intense search, during the 1980s, for a complementary non-food crop had shown that fibre hemp (Cannabis sativa) could be grown on Dutch farmland with considerable agricultural advantages. However, when Birgitte de Groot began her research within the framework given by The Dutch Hemp Programme about 10 years ago, the crucial question was, whether or not a hemp harvest could be used in any large-scale, industrial (non-food) application.
        The dissertation consists of the following chapters:

1. General Introduction.

2. Alkaline swelling of hemp woody core. (Published 1997 in J. Wood Chem. Technol. 17(1,2): 187-208)

3. Simplified kinetic modelling of alkaline delignification of hemp woody core. (Published 1994 in Holzforchung 48(3): 207-214)

4. Alkaline pulping of hemp woody core: kinetic modelling of lignin, xylan and cellulose extraction and degradation. (Published 1995 in Holzforchung 49(4): 332-342)

5. Alkaline woody core pulping: pulp and paper characteristics. (Accepted for publication in The Tappi Journal)

6. General discussion.

        The major part of the dissertation presents the results from her exploratory work in the laboratory, and is thus focused upon the possibility of using hemp woody core soda pulp for paper. The woody core, the inner 2/3 of the stalk, has usually been discarded or disposed of as a fuel, while the outer part (the bast) has been an important filament in the rope and yarn manufacturing industries for centuries. Chapters 2-5 report the results obtained. Each chapter (except nos 1 and 6) is written in the form of an article manuscript ready to publish, the majority of which had already been accepted by the time of the dissertation publication. The dissertation ends with a chapter, in which some quality aspects of hemp woody core soda pulp as a source of papermaking fibres are explored.

        Chapter 1: General Introduction. The dissertation starts with a review that covers subjects as diverse as plant anatomy, fibre morphology and fibre cell wall ultrastructure. It then introduces chemistry, the physics of porous solids, the fundamentals of polymer degradation, the concept of heterogenous reactions (particularly those between reactants in a liquid phase and reactants in a visco-elastic porous solid phase), the transport of degradation fragments out of the cell wall etc. In other words, the nature of swelling and the impact of changing porosity of plant tissue during impregnation and pulping.
        The striking similarities between the overall morphology and chemistry of hemp woody core and many hardwoods presently being used in the pulp and paper industry makes it to seem obvious that the use of non-woods in general and hemp woody core in particular (1) as a potential source of papermaking fibres, needs further investigation.

        Chapter 2: Alkaline swelling of hemp woody core. Reported is on an interesting study of the first stage of the pulping operation, the impregnation stage, during which the fibre cell walls swell and are filled with pulping liquor.
        By employing a multitude of rather sophisticated physico-chemical techniques, the author(s) conclude;
        • that the extent to which alkali swells the woody core tissue correlates well with the xylan:lignin ratio of that tissue [actually in support of the "spring (hydrophilic hemicellulose, expanding/swelling) and bar (hydrophobic lignin, rigid/ restricting) model", suggested by Stone and Scallan (2);
        • that this is the very first time evidence for the existance of 2-3 separate pore systems within the swollen fibre has been obtained [actually in support of the postulated existance of what was called "microreticular" and "macroreticular" pore systems within the cell wall, suggested by Stone and Scallan (3)];
        • that the material/hemicellulose/xylan removal and the increased pore sizes/pore volume in the swollen cell wall influences the subsequent course of component degradation/delignification and might therefore be necessary for fibre separation and fibrillation [actually in support of the idéas explicitly brought forward by Goring et al. (4)].

        Chapter 3: Simplified kinetic modelling of alkaline delignification of hemp woody core and Chapter 4: Alkaline pulping of hemp woody core: kinetic modelling of lignin, xylan and cellulose extraction and degradation. These constitute the central portion of the study and will therefore be treated together.
        Soda (aqueous NaOH) pulping (a common method of non-wood delignification) in a continuous flow reactor and quantitative analytical assessments of the component removal of hemp woody core at various stages of delignification resulted in sets of data that were fitted with good precision to exponential expressions. These expressions describe chemical reaction kinetics, i.e. the influence of temperature and duration on the extent and the rate of chemical reactions.
        The delignification of woody core by the soda method at reaction conditions similar to those prevailing in a laboratory continuous flow reactor (constant temperature, constant soda concentration and constant flow) demonstrated that
        • the removal of xylan (hemicellulose) facilitated the subsequent removal of lignin (see above);
        • the best fit to the experimental data was obtained if the three subsequent delignification modes (initial, bulk and rest/residual) that usually describe wood pulping were reduced to two and these were assumed to take place simultaneously rather than consecutively.
        In passing, a very important remark was made, that it is evident that the parameters in the kinetic expressions must be looked upon as being the mathematical expression of lumped overall reaction parameters.
        It is interesting to compare these results with those obtained for the kraft and soda delignification kinetics of wheat-straw in a batch reactor, as described by Lindgren et al. (5). Although the course of pulping in the latter study was fitted to a three stage delignification model, it was found that the wheat-straw lignin was removed to about 90% initially, and that only 1-2% was removed in the bulk stage. The similarities between the modes of delignification of these non-woods are striking. In comparison, only 15-20% of wood lignins are removed initially.
        The second central paper (Chapter 4) expands the kinetic expressions to describe the removal of lignin, xylan and cellulose during the course of soda pulping in a continuous flow reactor.
        The classic experimental techniques to study chemical reaction kinetics, either in a batch or a continuous flow set-up, are far from full-scale mill reality, as they are made under controlled and idealized conditions. They also have shortcommings as a means of getting detailed information about the multitude of complex, simultaneous physico-chemical reactions that are taking place. Not withstanding this, however, knowledge about the relative importance and influence of "lumped parameters of overall reaction patterns" is better than nothing. Ultimately it may lead to improved processes (6).

        Chapter 5 (Alkaline woody core pulping: pulp and paper characteristics).This is the final chapter of the dissertation containing experimental data and deals with the evaluation of the paper properties of hemp woody-core soda pulps.
        Again, by a ambitious comparison of data from (semi-empirical) physical testing of (apparent) bulk, e.g., tear resistance, tensile strength, burst strength, drainage resistance, brightness and opacity at different degrees of beating, with those obtained for some fundamental physico-chemical properties of the corresponding samples, such as the detailed chemical composition, and the molecular chain-length/polymerization degree [DP] and crystallinity of the cellulose, some very interesting and rarely seen relationships are examined.
        Based on the results obtained, the following observations and conclusions about hemp woody core pulp for paper may be drawn, although this was not always done in the dissertation. Qualitative comparison with hardwood pulp (Birch, Betula sp.) and agreement (=) and disagreement (±) with other non-woods has been made by the reviewer (7). Hemp soda pulp:
        • develops very high drainage resistance when beaten (=)
        • (apparent) bulk decreases on beating (=)
        • burst is linearly correlated with tensile (=)
        • tensile is adequate (=)
        • tear is (very) low (±,=)
        It was further demonstrated that for hemp soda pulp:
        • the impact on paper strength (tear) appeared to be negligable when DP is higher than 1000. [In other words the "rule of thumb" regarding paper strength was nicely confirmed];
        • the constant added to the rate equation for the degradation of cellulose (in terms of decreasing DP) found in the dissertation, suggested that a certain fraction of the cellulose, with ² 512 glucose units per cellulose polymer molecule, was more resistant to soda pulping than the rest of the cellulose [in close agreement with the "Fringed Micellar Model (8)].
        The most serious shortcomings of the dissertation are concentrated in Chapter 5, in which the important question concerning the value of hemp woody core soda pulp for paper is dealt.
        In spite of the multitude of measurements and data that are presented (although nowhere in the dissertation is listed a full set of original data for Chapter 5) many quite obvious and interesting lines of thoughts seems to be dropped "half way". For example, the DP/crystallinity effect on fibre and paper strength is not completed.
        Some further critical remarks can be made concerning the presentation of ‘s’ (the specific light scattering coefficient in the Kubelka-Munk theory) as applied to the interaction between light and a particulate sheet of pulp or paper, seems a bit confusing. The confusion arises from the basic question: is ‘s’ being caused by ALL the unbonded, free fibre surfaces in the sheet or is the opacity of a sheet (at equal brightness, or rather, constant ‘k’) dominated by the contribution to light reflection/scattering of the outer boundary surfaces of the sheet? An elucidating discussion concerning this and related questions can be found in the literature (9).

        Also in this dissertation:
         • the hemp woody core soda pulps were actually not compared (in terms of parallell experiments) with some "well accepted" hardwood, non-wood and/or recycled pulps;
        • the relevant long fibre - short fibre (hemp woody core soda pulps) mixtures for printing and writing papers were not studied.
        Without such or similar experiments, the "question/s" put forward in the introduction (whether or not hemp woody core soda pulp is suitable for printing and writing paper) can only be given an incomplete and indicative answer, viz:
        • "yes", incontrovertibly, the fibre hemp woody core can successfully be pulped by the soda method,
        • "maybe" the pulp is good enough as a short fibre component substituting for other easily available short fibre pulps (hardwood or non-wood) for printing and writing grades of paper.
        Hence, the above second crucial issue needs further investigation, which the "respondent" correctly points out in her dissertation: "Therefore it is conceivable to further develop alkaline woody core pulping for purposes as hardwood and straw pulp, as a component in pulp mixes for printing grade paper."

        Chapter 6: General discussion.
         The dissertation ends with a general discussion of the fundamental knowledge and state of the art of "alkaline hemp woody core pulping - impregnation characteristics, kinetic modelling and papermaking qualities", now including the results of the dissertation.
        Whether or not the results of the dissertation will ever come to practical use only future can tell. However, it contains some very interesting relationships and data, that immediately strengthen and widen our knowledge!

        Per Ahlgren
        Prof. Fibre properties
        Pulp & Paper Technology
        University of Karlstad
        Sweden
        E-mail: per.ahlgren@kau.se